“Vas U dere, Sharlie?” was how Jack Pearl closed his act. My sainted grandmother used to cry happy tears describing Jack Pearl’s comedy.
There are top-down and bottom-up strategies to origin of life. A top-down strategy might be based on analysis of sequences in living organisms to infer what occurred prior to LUCA (the last universal common (cellular) ancestor). The top-down analysis can be done for tRNA because pre-life tRNA (type I and type II) sequences are known with few ambiguities. As such, tRNA tells a story of pre-life on Earth (~4 billion years ago). TRNA sequence provides a historical record of pre-life on Earth that is straightforward to read.
A bottom-up strategy would be to generate life in a test tube from pre-life chemicals. Of course, many bottom-up experiments attempt to attack this difficult problem in smaller steps. From our top-down, sequence-based approach, we can make many suggestions for useful bottom-up experiments.
When top-down meets bottom-up, many issues regarding evolution of life on Earth are solved.
Our approach is top-down because we are molecular biologists, and sequence analysis is among our core interests. Largely, bottom-up approaches require modern big chemistry, which we do not have resources to do. We remain surprised that top-down approaches to origin of life are so powerful. We anticipated that most or all sequence data from pre-life would be overwritten by Darwinian selection. Pre-life tRNA sequences, however, were not overwritten. Pre-life tRNA sequences can be pulled up with a few clicks of a mouse using online data sets.
People consider LUCA in different ways. We consider LUCA to be among the first true organisms with an engulfing membrane, an intact DNA genome, perhaps modern ribosomes and perhaps a complete genetic code encoding 20 amino acids. Looking back ~4 billion years, LUCA is more of a concept than an organism. Many aspects of LUCA, however, remain accessible using top-down approaches.
FUCA might represent the first universal common ancestor prior to chemical evolution of LUCA. FUCA might have a fragmentary RNA genome, primitive protocells, polyglycine and then GADV (glycine, alanine, aspartic acid, valine) amyloids and coacervates, primitive pre-ribosomes, many polymers, proto-tRNA minihelices and a chemically evolving genetic code. As such, FUCA is more of a bottom-up problem, compared to LUCA, and neither FUCA nor LUCA are problems that have been solved adequately. The pathway from FUCA to LUCA is, so far, largely unknown. To progress from FUCA to LUCA requires solution of many problems including: 1) chiral sorting of nucleic acids and amino acids; 2) selection of A, G, C and U and rejection or segregation of other nucleotides; 3) progression of polymer world to minihelix world to tRNA world to tRNAomes; 4) chemical evolution of protocells; 5) sorting K+ and Na+; 6) amyloid and coacervate production; 7) modification of RNAs; 8) energy harnessing and generation; 9) chemical evolution of the genetic code; and 10) evolution of many ribozymes (i.e., ligase, exonuclease, endonuclease, helicase, RNA templated replicase, perhaps telomerase-like to synthesize RNA repeats, snap-back RNA primers (i.e., minihelices; tRNA), peptidyl transferase center (probably mobile), pre-16S rRNA decoding center, amino acid-AMP synthetase, aminoacyl-RNA, -minihelix, -tRNA transferase, others). Clearly, there are many engaging jobs for pre-life chemists.
Evolution of Life on Earth: tRNA, Aminoacyl-tRNA Synthetases and the Genetic Code